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[ CAS No. 35661-39-3 ] {[proInfo.proName]}

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Chemical Structure| 35661-39-3
Chemical Structure| 35661-39-3
Structure of 35661-39-3 * Storage: {[proInfo.prStorage]}
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Quality Control of [ 35661-39-3 ]

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Product Details of [ 35661-39-3 ]

CAS No. :35661-39-3 MDL No. :MFCD00037139
Formula : C18H17NO4 Boiling Point : -
Linear Structure Formula :HOCOCHCH3NH(CO2CH2C13H9) InChI Key :-
M.W : 311.33 Pubchem ID :-
Synonyms :

Calculated chemistry of [ 35661-39-3 ]

Physicochemical Properties

Num. heavy atoms : 23
Num. arom. heavy atoms : 12
Fraction Csp3 : 0.22
Num. rotatable bonds : 6
Num. H-bond acceptors : 4.0
Num. H-bond donors : 2.0
Molar Refractivity : 85.17
TPSA : 75.63 Ų

Pharmacokinetics

GI absorption : High
BBB permeant : Yes
P-gp substrate : No
CYP1A2 inhibitor : Yes
CYP2C19 inhibitor : No
CYP2C9 inhibitor : Yes
CYP2D6 inhibitor : No
CYP3A4 inhibitor : No
Log Kp (skin permeation) : -6.03 cm/s

Lipophilicity

Log Po/w (iLOGP) : 2.21
Log Po/w (XLOGP3) : 3.05
Log Po/w (WLOGP) : 3.0
Log Po/w (MLOGP) : 2.32
Log Po/w (SILICOS-IT) : 2.53
Consensus Log Po/w : 2.62

Druglikeness

Lipinski : 0.0
Ghose : None
Veber : 0.0
Egan : 0.0
Muegge : 0.0
Bioavailability Score : 0.56

Water Solubility

Log S (ESOL) : -3.68
Solubility : 0.0648 mg/ml ; 0.000208 mol/l
Class : Soluble
Log S (Ali) : -4.3
Solubility : 0.0154 mg/ml ; 0.0000496 mol/l
Class : Moderately soluble
Log S (SILICOS-IT) : -4.89
Solubility : 0.00396 mg/ml ; 0.0000127 mol/l
Class : Moderately soluble

Medicinal Chemistry

PAINS : 0.0 alert
Brenk : 0.0 alert
Leadlikeness : 0.0
Synthetic accessibility : 3.61

Safety of [ 35661-39-3 ]

Signal Word:Warning Class:N/A
Precautionary Statements:P261-P305+P351+P338 UN#:N/A
Hazard Statements:H302-H315-H319-H335 Packing Group:N/A
GHS Pictogram:

Application In Synthesis of [ 35661-39-3 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Upstream synthesis route of [ 35661-39-3 ]
  • Downstream synthetic route of [ 35661-39-3 ]

[ 35661-39-3 ] Synthesis Path-Upstream   1~14

  • 1
  • [ 1227363-07-6 ]
  • [ 28920-43-6 ]
  • [ 29022-11-5 ]
  • [ 35661-60-0 ]
  • [ 35661-39-3 ]
  • [ 35661-38-2 ]
  • [ 135248-89-4 ]
Reference: [1] Journal of Physical Chemistry B, 2010, vol. 114, # 19, p. 6751 - 6762
  • 2
  • [ 50-00-0 ]
  • [ 35661-39-3 ]
  • [ 84000-07-7 ]
Reference: [1] Bioorganic and Medicinal Chemistry, 2018, vol. 26, # 6, p. 1232 - 1238
  • 3
  • [ 35661-39-3 ]
  • [ 84000-07-7 ]
Reference: [1] European Journal of Organic Chemistry, 2013, # 21, p. 4509 - 4513
[2] Bioorganic and Medicinal Chemistry, 2016, vol. 24, # 6, p. 1163 - 1170
  • 4
  • [ 503-74-2 ]
  • [ 68858-20-8 ]
  • [ 35661-39-3 ]
  • [ 158257-40-0 ]
  • [ 26305-03-3 ]
YieldReaction ConditionsOperation in experiment
46%
Stage #1: With N-ethyl-N,N-diisopropylamine In dichloromethane for 3 h;
Stage #2: With piperidine In N,N-dimethyl-formamide for 0.1 h;
General procedure: 4.2 General procedure A: resin loading (0026) Solid phase peptide synthesis was conducted manually in a sinter-fitted polypropylene syringe. 2-Chlorotritylchloride (CTC) resin was preswelled in DCM (mL) for 15min and drained. The first amino acid in 0.4M DIPEA/DCM was added and the mixture was agitated for 3h. After draining the solvent, any free 2-CTC resin linkers were capped by treatment of the resin with a solution of 17:2:1 DCM/MeOH/DIPEA (3×3mL×5min), and subsequently with a solution of 8:1:1 DMF/DIPEA/acetic anhydride (2×3mL×10min). The resin was finally washed with DCM (2×3mL×1min), DMF (2×3mL×1min), DCM (2×3mL×1min) and DMF (2×3mL×1min). 4.3 General procedure B: Fmoc deprotection (0027) The resin was agitated with a solution of 10percent piperidine inDMF (2×3mL×3min) and subsequently washed with DMF(3×3mL×1min), DCM (3×3mL×1min), DMF (5×3mL×1min). The deprotected solutions were combined and diluted appropriately (100-fold for 0.05mmol resin loading). The resin loading was estimated by measuring the absorbance of the piperidine-fulvene adduct with 10percent piperidine in DMF as a reference (λ=301nm; ε=7800M−1cm−1). 4.4 General procedure C: peptide coupling with HBTU (0028) A solution was prepared of the appropriate Fmoc-protected amino acid (3 equiv. relative to resin loading) and HBTU (2.9 equiv. relative to resin loading) in minimum amount of DMF. DIPEA (6 equiv. relative to resin loading) was added and the resin was agitated for 1.5h. The resin was then drained and washed with DMF (3×3mL×1min), DCM (3×3mL×1min) and DMF (5×3mL×1min). 4.5 General procedure D: peptide coupling with HATU (0029) A solution was prepared of the appropriate Fmoc-protected amino acid (3 equiv. relative to resin loading) and HATU (2.9 equiv. relation to resin loading) in minimal DMF. DIPEA (6 equiv. relation to resin loading) was added to the solution and the mixture was immediately added to the resin and agitated. Reaction times were altered based on the residue being coupled: Phe(NMe) and Ala (2×2h); Thr and Sta (1×2h); Asn, Leu, D-Val and L-Val (2×2h); DMVal (3×3h). Once the reaction was complete, the resin was drained and washed with DMF (3×3mL×1min), DCM (3×3mL×1min) and DMF (3×3mL×1min). 4.6 General procedure E: peptide coupling with DIC (0030) A solution was prepared of the appropriate Fmoc-protected amino acid (1.5 equiv. relative to resin loading), HOBt (1.5 equiv. relative to resin loading) and DIC (1.5 equiv. relative to resin loading) in minimal DMF. This solution was stirred for 20min, then added to the resin and agitated overnight. The resin was drained and washed with DMF (3×3mL×1min), DCM (3×3mL×1min) and DMF (5×3mL×1min). Double coupling of the next amino acid after the coupling of the fluorinated amino acid was applied. 4.7 General procedure F: resin cleavage (0031) After the last Fmoc deprotection, the resin was washed with DMF (3×3mL×1min) and DCM (3×3mL×1min) then dried in vacuo. The resin was agitated with a solution of 95:2.5:2.5 TFA/TIS/H2O (3mL) for 2h. The resin was drained and washed with the same TFA mixture above (2×3mL×1min). The combined cleavage solutions were concentrated under a stream of nitrogen. Diethyl ether was added and the supernatant was decanted (3×). The residue was then dried in vacuo to provide the crude linear peptide
Reference: [1] Tetrahedron, 2018, vol. 74, # 12, p. 1278 - 1287
  • 5
  • [ 6066-82-6 ]
  • [ 35661-39-3 ]
  • [ 73724-40-0 ]
Reference: [1] Journal of Pharmaceutical Sciences, 1994, vol. 83, # 7, p. 999 - 1005
[2] Helvetica Chimica Acta, 2018, vol. 101, # 1,
[3] Journal of the American Chemical Society, 2003, vol. 125, # 45, p. 13680 - 13681
[4] Chemical Communications, 2009, # 4, p. 407 - 409
[5] Tetrahedron, 2009, vol. 65, # 19, p. 3871 - 3877
[6] Organic and Biomolecular Chemistry, 2011, vol. 9, # 11, p. 4182 - 4187
[7] Patent: WO2015/21092, 2015, A1, . Location in patent: Page/Page column 36
[8] Bioconjugate Chemistry, 2015, vol. 26, # 11, p. 2261 - 2278
[9] Patent: WO2015/187540, 2015, A1, . Location in patent: Page/Page column 22; 23
  • 6
  • [ 35661-39-3 ]
  • [ 73724-40-0 ]
Reference: [1] Patent: US6759509, 2004, B1,
  • 7
  • [ 67-56-1 ]
  • [ 35661-39-3 ]
  • [ 146346-88-5 ]
Reference: [1] Journal of Organic Chemistry, 2014, vol. 79, # 12, p. 5420 - 5431
[2] The Journal of organic chemistry, 2002, vol. 67, # 24, p. 8291 - 8298
  • 8
  • [ 70-25-7 ]
  • [ 35661-39-3 ]
  • [ 146346-88-5 ]
Reference: [1] Synthetic Communications, 2003, vol. 33, # 11, p. 1815 - 1820
  • 9
  • [ 35661-39-3 ]
  • [ 146346-88-5 ]
Reference: [1] Synlett, 2018, vol. 29, # 3, p. 301 - 305
  • 10
  • [ 35661-39-3 ]
  • [ 146803-41-0 ]
Reference: [1] Tetrahedron, 2007, vol. 63, # 28, p. 6577 - 6586
[2] Journal of Organic Chemistry, 2001, vol. 66, # 3, p. 697 - 706
[3] Journal of Organic Chemistry, 1993, vol. 58, # 8, p. 2313 - 2316
[4] Organic and Biomolecular Chemistry, 2011, vol. 9, # 19, p. 6566 - 6574
[5] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 2, p. 1187 - 1188
[6] Angewandte Chemie - International Edition, 2013, vol. 52, # 23, p. 6006 - 6010[7] Angew. Chem., 2013, vol. 125, # 23, p. 6122 - 6126
  • 11
  • [ 35661-39-3 ]
  • [ 161529-13-1 ]
YieldReaction ConditionsOperation in experiment
88%
Stage #1: With 2,4,6-tripropyl-1,3,5,2,4,6-trioxatriphosphinane-2,4,6-trioxide; N-ethyl-N,N-diisopropylamine In ethyl acetate at 0℃; for 0.166667 h;
Stage #2: With sodium tetrahydroborate In water; ethyl acetate at 0℃; for 0.416667 h;
General procedure: To a solution of carboxylic acid (10 mmol) in THF (10 mL), DIPEA (11 mmol, 1.42 mL) and 50percent T3P in EtOAc (20 mmol, 6.36 mL) were added at 0 °C and the solution was stirred for about 10 min. Then aqueous solution of NaBH4 (10 mmol, 388 mg in 0.3 mL of H2O) was added to the reaction mixture at the same temperature and the reaction was allowed to stir till the completion of the reaction as indicated by TLC. After the completion of the reaction, the solvent was evaporated and the crude alcohol was extracted into EtOAc and the organic phase was washed with 5percent citric acid (10 mL .x. 2), 5percent Na2CO3 (10 mL .x. 2), water, and brine solution. The product was isolated after the evaporation of solvent under reduced pressure and dried over anhydrous Na2SO4.
88%
Stage #1: With 1-[(1-(cyano-​2-​ethoxy-​2-​oxoethylidenaminooxy)​dimethylamino-​morpholino)]-uronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 0℃; for 0.333333 h;
Stage #2: With sodium tetrahydroborate In water; N,N-dimethyl-formamide at 0℃; for 0.0833333 h;
To an ice cold solution of Fmoc-Ala-OH (1 mmol) and DIPEA (1.2 mmol) in DMF (5 mL) at 0 °C, COMU (1.1 mmol) was added.
The reaction mixture was stirred for 20 min.
Then, NaBH4 (1 mmol) in water was added to the reaction mixture and stirred at the same temperature for 5 min.
The reaction mixture was taken into ethyl acetate (15 mL).
The organic layer was successively washed with 10percent HCl (2 * 10 mL), 10percent aqueous sodium carbonate (3 * 10 mL) and brine (3 * 10 mL).
Then the product was dried over anhydrous Na2SO4, and the solvent was evaporated under a reduced pressure.
The residue was purified by column chromatography using ethyl acetate-hexane (30:70) as an eluent.
Reference: [1] Journal of Organic Chemistry, 2001, vol. 66, # 25, p. 8454 - 8462
[2] Tetrahedron Letters, 2000, vol. 41, # 32, p. 6131 - 6135
[3] Tetrahedron Letters, 2012, vol. 53, # 38, p. 5059 - 5063
[4] Journal of Molecular Liquids, 2014, vol. 198, p. 94 - 100
[5] RSC Advances, 2014, vol. 4, # 87, p. 46947 - 46950
[6] European Journal of Organic Chemistry, 2015, vol. 2015, # 28, p. 6341 - 6350
[7] Organic and Biomolecular Chemistry, 2011, vol. 9, # 11, p. 4182 - 4187
[8] Journal of Organic Chemistry, 2009, vol. 74, # 15, p. 5260 - 5266
[9] Synthetic Communications, 2009, vol. 39, # 19, p. 3555 - 3566
[10] Organic and Biomolecular Chemistry, 2011, vol. 9, # 11, p. 4182 - 4187
[11] ACS Combinatorial Science, 2017, vol. 19, # 3, p. 131 - 136
  • 12
  • [ 35661-39-3 ]
  • [ 456-47-3 ]
  • [ 211617-68-4 ]
  • [ 133865-89-1 ]
Reference: [1] Journal of Medicinal Chemistry, 2007, vol. 50, # 20, p. 4909 - 4916
  • 13
  • [ 35661-39-3 ]
  • [ 193954-26-6 ]
Reference: [1] Helvetica Chimica Acta, 1998, vol. 81, # 2, p. 187 - 206
[2] Helvetica Chimica Acta, 1998, vol. 81, # 1, p. 59 - 65
  • 14
  • [ 35661-39-3 ]
  • [ 87512-31-0 ]
YieldReaction ConditionsOperation in experiment
78%
Stage #1: With N-ethyl-N,N-diisopropylamine In dichloromethane at 20℃; for 2.73333 h;
Stage #2: With piperidine In N,N-dimethyl-formamide at 20℃;
A solution of Fmoc-l-Ala-OH (0.93 g, 3.0 mmol) in CH2Cl2 (25 mL) was added to 2-chlorotrityl chloride resin (6 g, loading at 0.5 mmol/g), followed by DIPEA (0.52 mL, 3.0 mmol).
After the resin mixture was agitated for 14 min, DIPEA (0.78 mL, 4.5 mmol) was added and the mixture was further shaken for 2.5 h.
The solution was drained off and the resin was washed with DMF (20 mL).
A solution of CH2Cl2/MeOH/DIPEA (40 mL, 80:15:5) was added to the mixture and shaken for 30 min.
The solution was drained and the procedure was repeated.
The resin was then washed with DMF (20 mL).
Piperidine in DMF (15.0 mL, 1:4) was added to the resin mixture and shaken for 10 min.
The liquid was drained off and piperidine washing was repeated for another 40 min.
The amino acid-loaded resin was thoroughly washed with DMF (35 mL), isopropanol (35 mL) and n-hexane (35 mL).
The resin was then dried under vacuum for 30 min and placed in a desiccator overnight. CH2Cl2 (50 mL) was added to the resin and left for 1 h.
The solution was drained and a solution of HBTU (4.27 g, 11.25 mmol), HOBt (1.72 g, 11.25 mmol), Fmoc-l-Ala-OH (2.34 g, 7.5 mmol) and DIPEA (2.61 mL, 15.0 mmol) in DMF (11.3 mL) was added.
The amino acid resin mixture was agitated for 4 h.
The solution was then drained and washed with DMF (30 mL), isopropanol (30 mL) and n-hexane (30 mL).
2,2,2-Trifluroethanol in CH2Cl2 (15 mL, 1:4) was added to the amino acid-loaded resin and agitated for 2 h.
The solution was drained and the organic solvent removed in vacuo to afford 22 (0.90 g, 78percent) as a yellow foam. m.p. 195-196 °C; Rƒ 0.53 (CH2Cl2/MeOH 9:1); [α]D20 -23.9 (c 0.14, MeOH); IR (ATR) νmax 3297, 2918, 1692, 1650, 1533, 1450, 1318, 1229 cm-1; 1H NMR (CDCl3, 500 MHz) δ 8.09 (1H, d, J = 7.2 Hz, NH-5), 7.89 (2H, d, J = 7.4 Hz, 2H-FmocAr), 7.74 (1H, d, J = 7.4 Hz, 1H-FmocAr), 7.72 (1H, d, J = 7.4 Hz, 1H-FmocAr), 7.50 (1H, d, J = 7.5 Hz, NH-1), 7.41 (2H, t, J = 7.4 Hz, H-FmocAr), 7.33 (2H, td, J = 7.4, 0.9 Hz, 2H-FmocAr), 4.27-4.15 (4H, m, CO2CH2CH, CO2CH2CH, H-6), 4.08 (1H, d, J = 7.5, 7.2 Hz, H-2), 1.27 (3H, d, J = 7.3 Hz, H3-7), 1.22 (3H, d, J = 7.2 Hz, H3-3); 13C NMR (CDCl3, 125 MHz) δ 174.2 (C-8), 172.2 (C-4), 155.6 (CO2CH2CH), 143.9 (C-FmocAr), 143.8 (C-FmocAr), 140.7 (2C-FmocAr), 127.6 (2C-FmocAr), 127.1 (2C-FmocAr), 125.3 (2C-FmocAr), 120.1 (2C-FmocAr), 65.6 (CO2CH2CH), 49.7 (C-2), 47.5 (C-6), 46.7 (CO2CH2CH), 18.2 (C-3), 17.3 (C-7); (+)-HRESIMS [M+Na]+ 405.1424 (calcd. for C21H22NaN2O5, 405.1421).
Reference: [1] Tetrahedron, 2018, vol. 74, # 48, p. 6929 - 6938
[2] Journal of the American Chemical Society, 2014, vol. 136, # 10, p. 3919 - 3927
[3] Patent: WO2015/187540, 2015, A1,
[4] Patent: EP3184540, 2017, A1,
[5] Angewandte Chemie - International Edition, 2017, vol. 56, # 50, p. 15984 - 15988[6] Angew. Chem., 2017, vol. 129, # 50, p. 16200 - 16204,5
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